Author/Authors :
Li, Weiyue Department of Medical Imaging Centre - Nanfang Hospital - Southern Medical University - Guangzhou, China , Xiao, Xiang Department of Medical Imaging Centre - Nanfang Hospital - Southern Medical University - Guangzhou, China , Li, Xiaodan Department of Medical Imaging Centre - Nanfang Hospital - Southern Medical University - Guangzhou, China , Xu, Yikai Department of Medical Imaging Centre - Nanfang Hospital - Southern Medical University - Guangzhou, China , Ma, Lichao Department of Medical Imaging Centre - Nanfang Hospital - Southern Medical University - Guangzhou, China , Guo, Liuji Department of Medical Imaging Centre - Nanfang Hospital - Southern Medical University - Guangzhou, China , Yan, Chenggong Department of Medical Imaging Centre - Nanfang Hospital - Southern Medical University - Guangzhou, China , Wu, Yuankui Department of Medical Imaging Centre - Nanfang Hospital - Southern Medical University - Guangzhou, China
Abstract :
To investigate the potential of L5 peptide-guided pretargeting approach to identify GPC3-expressing hepatocellular
carcinoma (HCC) using ultrasmall superparamagnetic iron oxide (USPIO) as the MR probe. Methods. Immunofluorescence with
carboxyfluorescein- (FAM-) labeled L5 peptide was performed in HepG2 cells. Polyethylene glycol-modied USPIO (PEGUSPIO) and its conjugation with streptavidin (SA-PEG-USPIO) were synthesized, and their hydrodynamic diameters, zeta
potential, T2 relaxivity, and cytotoxicity were measured. In vitro and in vivo two-step pretargeting MR imaging was performed on
HepG2 cells and tumor-bearing mice after the administration of biotinylated L5 peptide (rst step), followed by SA-PEG-USPIO
(second step). Prussian blue staining was performed to assess iron deposition in tumors. Results. e high specicity of L5 peptide
for GPC3 was demonstrated. Generation of SA-PEG-USPIO nanoparticles with good biocompatibility (an average hydrodynamic
diameter of 35.97 nm and a zeta potential of −7.91 mV), superparamagnetism (R2 = 0.1039 ×103 mM−1
s
−1
), and low toxicity was
achieved. e pretargeting group showed more enhancement than the nonpretargeting group both in vitro (60% vs 20%, P < 0.05)
and in vivo (32% vs 6%, P < 0.001). Substantial iron deposition was only observed in HepG2 cells and tumors in the pretargeting
group. Conclusion. L5 peptide-guided, two-step pretargeting approach with USPIO as the MR imaging probe is a lucrative strategy
to specically identify GPC3-expressing HCC.
